Juhyun Song

The protective effect of melatonin on neural stem cell against LPS-induced inflammation

Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs). Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO) production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases.

Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model

Purpose Alzheimers disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. Materials and Methods We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 µL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. Results Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and γ-glutamyl cysteine synthetase, in the STZ-Agm group. Conclusion Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.

Resveratrol Induces the Expression of Interleukin-10 and Brain-Derived Neurotrophic Factor in BV2 Microglia under Hypoxia

Microglia are the resident macrophages of the central nervous system (CNS) and play an important role in neuronal recovery by scavenging damaged neurons. However, overactivation of microglia leads to neuronal death that is associated with CNS disorders. Therefore, regulation of microglial activation has been suggested to be an important target for treatment of CNS diseases. In the present study, we investigated the beneficial effect of resveratrol, a natural phenol with antioxidant effects, in the microglial cell line, BV2, in a model of hypoxia injury. Resveratrol suppressed the mRNA expression of the pro-inflammatory molecule, tumor necrosis factor-α, and promoted the mRNA expression of the anti-inflammatory molecule, interleukin-10, in BV2 microglia under hypoxic conditions. In addition, resveratrol inhibited the activation of the transcription factor, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), which is upstream in the control of inflammatory reactions in hypoxia-injured BV2 microglia. Moreover, resveratrol promoted the expression of brain-derived neurotrophic factor (BDNF) in BV2 microglia under hypoxic stress. Overall, resveratrol may promote the beneficial function of microglia in ischemic brain injury.

Apoptosis Signal Regulating Kinase 1 (ASK1): Potential as a Therapeutic Target for Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia, characterized by a decline in memory and cognitive function. Clinical manifestations of AD are closely associated with the formation of senile plaques and neurofibrillary tangles, neuronal loss and cognitive decline. Apoptosis signal regulating kinase 1 (ASK1) is a mediator of the MAPK pathway, which regulates various cellular responses such as apoptosis, cell survival, and differentiation. Accumulating evidence indicates that ASK1 plays a key role in the pathogenesis of neurodegenerative disorders such as Huntington’s disease and AD. Of particular interest, ASK1 is associated with many signaling pathways, which include endoplasmic reticulum (ER) stress-mediated apoptosis, Aβ-induced neurotoxicity, tau protein phosphorylation, and insulin signal transduction. Here, we review experimental evidence that links ASK1 signaling and AD pathogenesis and propose that ASK1 might be a new point of therapeutic intervention to prevent or treat AD.

Treatment of FGF-2 on stem cells from inflamed dental pulp tissue from human deciduous teeth

OBJECTIVE The purposes of this study were to isolate and characterize stem cells from inflamed pulp tissue of human functional deciduous teeth (iSHFD) and to evaluate the influence of fibroblastic growth factor-2 (FGF-2) on the regenerative potential. MATERIALS AND METHODS We successfully isolated mesenchymal stem cells (MSCs) from the inflamed dental pulp tissue of human deciduous teeth and demonstrated that their regenerative potential could be enhanced by the application of FGF-2 (20 ng ml(-1)) during ex vivo expansion. Isolated stem cells expanded in FGF-2 were characterized using a colony-forming assay, proliferation, migration, in vitro differentiation, in vivo ectopic transplantation assay, and gene expression profiling. RESULTS MSCs isolated from the inflamed pulp tissue of functional deciduous teeth potentially possess the qualities of those from human exfoliated deciduous teeth. FGF-2 applied to iSHFD during expansion enhanced the colony-forming efficiency of these cells, increased their proliferation and migration potential, and reduced their differentiation potential in vitro. However, the ectopic transplantation of iSHFD/FGF-2 in vivo increased the formation of dentin-like material. CONCLUSION FGF-2 expansion of stem cells from inflamed pulp tissues of human deciduous teeth can be a good source of stem cells for future clinical applications and a novel way of using discarded inflamed tissues.

miR-155 is involved in Alzheimer's disease by regulating T lymphocyte function

Alzheimer’s disease (AD) is considered the most common cause of sporadic dementia. In AD, adaptive and innate immune responses play a crucial role in clearance of amyloid beta and maintenance of cognitive functions. In addition to other changes in the immune system, AD alters the T-cell responses that affect activation of glial cells, neuronal cells, macrophages, and secretion of pro-inflammatory cytokines. These changes in the immune system influence AD pathogenesis. Micro-RNA (miRNA)-155 is a multifunctional miRNA with a distinct expression profile. It is involved in diverse physiological and pathological mechanisms, such as immunity and inflammation. Recent studies indicate that miR-155 regulates T-cell functions during inflammation. In this article, we summarize recent studies describing the therapeutic potential of miR-155 via regulation of T cells in AD. Further, we propose that regulation of miR-155 might be a new protective approach against AD pathogenesis.

Adiponectin as a new paradigm for approaching Alzheimer's disease

Adiponectin is an adipocytokine released by the adipose tissue and has multiple roles in the immune system and in the metabolic syndromes such as cardiovascular disease, Type 2 diabetes, obesity and also in the neurodegenerative disorders including Alzheimers disease. Adiponectin regulates the sensitivity of insulin, fatty acid catabolism, glucose homeostasis and anti-inflammatory system through various mechanisms. Previous studies demonstrated that adiponectin modulates memory and cognitive impairment and contributes to the deregulated glucose metabolism and mitochondrial dysfunction observed in Alzheimers disease. Here, we aim to summarize recent studies that suggest the potential correlation between adiponectin and Alzheimers disease.

The Beneficial Effect of Melatonin in Brain Endothelial Cells against Oxygen-Glucose Deprivation Followed by Reperfusion-Induced Injury

Melatonin has a cellular protective effect in cerebrovascular and neurodegenerative diseases. Protection of brain endothelial cells against hypoxia and oxidative stress is important for treatment of central nervous system (CNS) diseases, since brain endothelial cells constitute the blood brain barrier (BBB). In the present study, we investigated the protective effect of melatonin against oxygen-glucose deprivation, followed by reperfusion- (OGD/R-) induced injury, in bEnd.3 cells. The effect of melatonin was examined by western blot analysis, cell viability assays, measurement of intracellular reactive oxygen species (ROS), and immunocytochemistry (ICC). Our results showed that treatment with melatonin prevents cell death and degradation of tight junction protein in the setting of OGD/R-induced injury. In response to OGD/R injury of bEnd.3 cells, melatonin activates Akt, which promotes cell survival, and attenuates phosphorylation of JNK, which triggers apoptosis. Thus, melatonin protects bEnd.3 cells against OGD/R-induced injury.

P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP

The short isoform of ErbB3-binding protein 1 (Ebp1), p42, is considered to be a potent tumor suppressor in a number of human cancers, although the mechanism by which it exerts this tumor-suppressive activity is unclear. Here, we report that p42 interacts with the cSH2 domain of the p85 subunit of phosphathidyl inositol 3-kinase (PI3K), leading to inhibition of its lipid kinase activity. Importantly, we found that p42 induces protein degradation of the p85 subunit and further identified HSP70/CHIP complex as a novel E3 ligase for p85 that is responsible for p85 ubiquitination and degradation. In this process, p42 couples p85 to the HSP70/CHIP-mediated ubiquitin–proteasomal system (UPS), thereby promoting a reduction of p85 levels both in vitro and in vivo. Thus, the tumor-suppressing effects of p42 in cancer cells are driven by negative regulation of the p85 subunit of PI3K.

Association between Risk Factors for Vascular Dementia and Adiponectin

Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.